A nucleic acid such as small interfering RNA (siRNA), micro RNA (miRNA), a short hairpin RNA or small hairpin RNA (shRNA) expression vector, or antisense oligonucleotide is a nucleic acid that induces sequence-specific gene expression inhibition in vivo and is known as nucleic acid medicine.
In the field of nucleic acid medicine, particularly, siRNA has been attracting attention. siRNA is double-stranded RNA formed of 19 to 23 base pairs and induces sequence-specific gene expression inhibition referred to as RNA interference (RNAi).
Although siRNA is chemically stable, siRNA has problems as therapeutic applications since siRNA is easily decomposed by ribonuclease (RNase) in blood plasma and siRNA is unlikely to penetrate a cell membrane by itself (for example, see PTL 1).
For the above-described problems, it is known that by encapsulating siRNA in a fine particle containing a cationic lipid, the encapsulated siRNA is protected from decomposition in blood plasma and can penetrate a lipophilic cell membrane (for example, see PTL 1).
Further, PTLs 2 to 4 describe a cationic lipid that is used to deliver nucleic acid medicine such as siRNA and has improved biodegradability.
Further, fine particles containing a cationic lipid have a stability problem in that they are prone to aggregation during a storage period, and a method of suppressing aggregation by allowing a polyethylene glycol-modified lipid (PEG lipid) to be contained in the fine particles is known to solve this problem. Further, a method of suppressing aggregation and improving efficiency of nucleic acid delivery by using PEG-DPG; which is a specific PEG lipid, as a constituent component of fine particles or by using a formulation formed of PEG-DPG with the fine particles and a deionized solvent is described in PTL 5.